1. Field of the Invention
The present invention relates generally to devices and methods for analyzing samples in microfluidic cartridges, and, in particular, to a device for analyzing sample solutions such as whole blood based on coagulation and agglutination which requires no external power source or moving parts.
2. Description of the Related Art
Microfluidic devices have recently become popular for performing analytical testing. Using tools developed by the semiconductor industry to miniaturize electronics, it has become possible to fabricate intricate fluid systems which can be inexpensively mass produced. Systems have been developed to perform a variety of analytical techniques for the acquisition of information for the medical field.
In microfluidic channels, fluids usually exhibit laminar behavior. U.S. Pat. No. 5,716,852, which patent is herein incorporated by reference in its entirety, is an example of such a device. This patent teaches a microfluidic system for detecting the presence of analyte particles in a sample stream using a laminar flow channel having at least two input channels which provide an indicator stream and a sample stream, where the laminar flow channel has a depth sufficiently small to allow laminar flow of the streams and length sufficient to allow diffusion of particles of the analyte into the indicator stream to form a detection area, and having an outlet out of the channel to form a single mixed stream. This device, which is known as a T-Sensor, allows the movement of different fluidic layers next to each other within a channel without mixing other than by diffusion. A sample stream, such as whole blood, and a receptor stream, such as an indicator solution, and a reference stream, which is a known analyte standard, are introduced into a common microfluidic channel within the T-Sensor, and the streams flow next to each other until they exit the channel. Smaller particles, such as ions or small proteins, diffuse rapidly across the fluid boundaries, whereas larger molecules diffuse more slowly. Large particles, such as blood cells, show no significant diffusion within the time the two flow streams are in contact.
Two interface zones are formed within the microfluidic channel between the fluid layers. The ratio of a detectable property, such as fluorescence intensity, of the two interface zones is a function of the concentration of the analyte, and is largely free from cross-sensitivities to other sample components and instrument parameters.
Usually, microfluidic systems require some type of external fluidic driver to function, such as piezoelectric pumps, micro-syringe pumps, electroosmotic pumps, and the like. In U.S. patent application Ser. No. 09/415,404, which application is assigned to the assignee of the present invention and is hereby incorporated by reference, microfluidic systems are described which are totally driven by inherently available internal forces such as gravity, capillary action, absorption by porous material, chemically induced pressures or vacuums, or by vacuum or pressure generated by simple manual action upon a power source located within the cartridge. Such devices are extremely simple and inexpensive to manufacture and do not require electricity or any other external power source for operation. Such devices can be manufactured entirely out of a simple material such as plastic, using standard processes like injection molding or laminations. In addition, microfluidic devices of this type are very simple to operate.
microfluidic devices of this type described can be used to qualitatively or semi-quantitatively determine analyte concentrations, to separate components from particulate-laden samples such as whole blood, or to manufacture small quantities of chemicals.
A practical use of these microfluidic devices could be in the determination of several parameters directly in whole blood. A color change in the diffusion zone of a T-Sensor detection channel can provide qualitative information about the presence of the analyte. This method can be made semi-quantitative by providing a comparator color chart with which to compare the color of the diffusion zone, similar to using a paper test strip, but with greate control and reproducibility.
It would be desirable, in many situations, to produce a device for analyzing samples in microfluidic channels based on coagulation or agglutination as a function of contact between sample analyte particles and reagent particles. An example of such an assay would be the determination of a person""s blood group by bringing a drop of blood into contact with one or more antisera on a disposable microfluidic cartridge, and visually observing the flow behavior of these two solutions as they flow adjacent to each other, or mixed through sedimentation as they flow with each other through microfluidic channels. If a reaction occurs, the flow will either slow down, stop, or show another observable change that can be attributed to coagulation or agglutination.
The accuracy of the device can be enhanced by the addition of a readout system which may consist of an absorbance, fluorescence, chemiluminescence, light scatter, or turbidity detector placed such that the detector can observe an optically observable change caused by the presence or absence of a sample analyte or particle in the detection channel. Alternatively, electrodes can be placed within the device to observe electrochemically observable changes caused by the presence or absence of a sample analyte or particle within the detection channel.
Accordingly, it is an object of the present invention to provide a microfluidic device which is capable of performing diagnostic assays without the use of an external power source.
It is a further object of the present invention to provide a disposable cartridge for analyzing fluid samples which is inexpensive to produce and simple to operate.
It is another object of the present invention to provide a microfluidic analysis cartridge in which a visual analysis can be made of the sample reaction.
These and other objects are accomplished in the present invention by a simple cartridge device containing microfluidic channels which perform a variety of analytical techniques based on coagulation or agglutination without the use of external driving forces applied to the cartridge. Single disposable cartridges for performing blood typing assays can be constructed using this technology.